The use of cyclodextrins as a complexing agent for materials is known. For example, the following U.S. Patents disclose the use of cyclodextrins to complex actives: U.S. Pat. Nos. 4,296,137, 4,296,138 and 4,348,416 to Borden (flavoring material for use in chewing gum, dentifrices, cosmetics, etc.); 4,265,779 to Gandolfo et al. (suds suppressors in detergent compositions); 3,816,393 and 4,054,736 to Hyashi et al. (prostaglandins for use as a pharmaceutical); 3,846,551 to Mifune et al. (insecticidal and acaricidal compositions); 4,024,223 to Noda et al. (menthol, methyl salicylate, and the like); 4,073,931 to Akito et al. (nitro-glycerine); 4,228,160 to Szjetli et al. (indomethacin); 4,247,535 to Bernstein et al. (complement inhibitors); 4,268,501 to Kawamura et al. (anti-asthmatic actives); 4,365,061 to Szjetli et al. (strong inorganic acid complexes); 4,371,673 to Pitha (retinoids); 4,380,626 to Szjetli et al. (hormonal plant growth regulator), 4,438,106 to Wagu et al. (long chain fatty acids useful to reduce cholesterol); 4,474,822 to Sato et al. (tea essence complexes); 4,529,608 to Szjetli et al. (honey aroma), 4,547,365 to Kuno et al. (hair waving active-complexes); 4,596,795 to Pitha (sex hormones); 4,616,008 Hirai et al. (antibacterial complexes); 4,636,343 to Shibanai (insecticide complexes), 4,663,316 to Ninger et al. (antibiotics); 4,675,395 to Fukazawa et al. (hinokitiol); 4,732,759 and 4,728,510 to Shibanai et al. (bath additives); 4,751,095 to Karl et al. (aspartamane); 4,560,571 (coffee extract); 4,632,832 to Okonogi et al. (instant creaming powder) 5,571,782 and 5,635,238 to Trinh et al. (perfumes, flavors, and pharmaceuticals).
Cyclodextrins complexes are particularly desirable when the active is a flavoring material. By complexing the flavoring material with a cyclodextrin the flavor material is protected from degradation as a result of reactions induced by heat, light, and/or reaction with oxygen or other compounds. For example, .gamma.-terpinene is a reactive terpene that is important in tangerine flavors. .gamma.-terpinene is, however, easily oxidized to p-cymene which has an unpleasant kerosene note. By complexing the .gamma.-terpinene with cyclodextrin the compound is protected from the adverse effects of oxygen and provides a flavor that is stable for a much longer period of time.
Complexing the flavoring material with a cyclodextrin also reduces loss of the flavor material by volatilization and/or sublimation. For example, diacetyl is a volatile compound that has a butter flavor. Due to its volatility the butter flavor is readily lost when food products containing diacetyl are heated. Complexing the diacetyl with cyclodextrin, however, leads to less butter flavor being lost when the food product is cooked in a microwave.
In addition, cyclodextrin complexes provide stable, standardized powders containing the active that are easy to use. Being a powder, the cyclodextrin complexes are easy to measure, handle, and store. The increased stability of the flavor when complexed with cyclodextrin provides a flavor material that can be stored longer. As a result of the improved stability measuring amounts of the flavor is more precise since the flavor content remains more constant over time. The longer storage times, easy handling, and simplicity of use all reduce costs and thus are of commercial importance in the food industry. A further economic benefit of using cyclodextrin complexes is that less of the cyclodextrin complex is needed to flavor food compared to the natural spice or flavor.
Yet another advantage of cyclodextrin complexes is that the natural material content of some flavors can be reduced by complexing the flavor component(s) with cyclodextrin and thus the risk of allergic reactions is minimized and the risk of microbial contamination is reduced.
The content of the flavor in conventional cyclodextrin complexes typically ranges from about 5 to 15 percent, and more often from 7 to 10 percent. Flavors typically consist of more than one component and while it is possible to complex all the components of the flavor composition with a cyclodextrin, generally only the more vulnerable components of the flavor composition are complexed. Specific flavors and or flavor enhancers include, for example, those disclosed in U.S. Pat. Nos. 4,348,416 and 5,571,782.
Specific examples of flavors complexed with cyclodextrin include: U.S. Pat. No. 4,560,571 to Sato et al. that discloses an instant beverage in which soluble flavors and aromatic components present in roasted coffee beans, roasted beans, or roasted cereal are complexed with cyclodextrins; U.S. Pat. No. 4,529,608 to Szejtli et al. that discloses a process for the preparation of honey powder that preserves the aroma substance of the honey by complexing the aroma components with cyclodextrin; U.S. Pat. No. 3,061,444 to Rogers et al. that discloses complexing meat and vegetable aromas with cyclodextrin; U.S. Pat. No. 4,001,438 to Marmo et al. that discloses peppermint cyclodextrin complexes for flavoring chewing gum; and U.S. Pat. No. 3,140,184 to Robbins et al. that discloses acetaldehyde/diethylacetate cyclodextrin complexes.
Complexing the flavor with cyclodextrin does not adversely effect the flavor, texture, or appearance of the food. In fact, in some instances the food texture may actually be improved by complexing the flavor with a cyclodextrin. For example, soups and drinks prepared from mixes may be beneficially thickened when the flavor is complexed with a cyclodextrin.
Cyclodextrins are obtained by the action of the enzyme cycloglycosyltransferase on starches. In dilute aqueous solutions the enzyme connects the naturally occurring helixes in starch to form 3-dimensional polyglucose rings or crowns. Cyclodextrins are polyglucose rings created with 6, 7, or 8 glucose units and are referred to as .alpha., .beta., or .gamma. cyclodextrins, respectively. The external part of the crown like structure consists of primary and secondary hydroxyl groups and is hydrophilic. The internal part of the crown consists mainly of carbon and hydrogen atoms and ether linkages and forms a hydrophobic cavity. This macrocyclic structure with a hydrophilic exterior and hydrophobic interior allows the cyclodextrin molecule to form inclusion complexes with a wide variety of chemically different compounds referred to herein as actives. The cyclodextrin behaves like a "host" that can accommodate, and release, the active or "guest" molecule.
A variety of methods are known to form cyclodextrin complexes. All these methods involve contacting the active with the cyclodextrin to form the complex. Typically, a warm aqueous solution of the cyclodextrin molecule is mixed with the active for sufficient time for the complex to form, followed by removal of the aqueous solvent. Alternatively, complexation can take place in an organic solvent or an aqueous solvent containing an organic cosolvent. Representative organic solvents include ethanol, isopropanol, acetone, and ethylacetate. In another method, the active is combined with a small amount of solvent to form a paste and the cyclodextrin and paste are kneaded together to form the complex, followed by drying the resulting complex. This method is commonly used when a high ratio of active to cyclodextrin is required. Once the cyclodextrin complex is formed a variety of methods are available to dry it. Typically, the complex is filtered to remove the solvent and air-dried, dried in a vacuum oven, or freeze dried. The complex may also be isolated by spray drying.
All of the methods for forming cyclodextrin complexes involve an equilibrium between the active complexed with the cyclodextrin, i.e., the complex, and the free active, i.e., the active not complexed with the cyclodextrin. Thus, a specific amount of free active is always present. When isolating the complex, any free active is lost during the filtering and/or drying steps, and thus, the efficiency of the process is much less than 100%. The efficiency of the process is measured as the percent yield for incorporation of the active, i.e., the amount of active recovered as a cyclodextrin complex divided by the starting amount of active. For example, the efficiency is generally only about 30 percent when cyclodextrin complexes are recovered by spray drying. Thus, when spray drying cyclodextrin complexes, substantially more than 50 percent of the active can be lost during the drying step. This loss of active increases the cost of the final product and is especially problematic for expensive actives.
Furthermore, the expense of cyclodextrins and thus the cost of the resulting cyclodextrin complexes have limited their commercial use. As a result, although cyclodextrin complexes of various actives have been disclosed and set forth in the art, their commercial use has been limited. Thus, there remains a need to reduce the cost of producing cyclodextrin complexes so that they can be commercially valuable. The present invention resolves this need.